Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death in the United States showing a rapid clinical course leading to death. Once diagnosed, PDAC has a median survival of 6 months and a 5-year survival rate of only 3 percent (Li et al., Lancet 363:1049-1057 (2004)).
As chemotherapy and radiotherapy have only modest benefits, and surgery is only possible in 20% of patients, early detection that allows surgical resection offers the best hope for longer survival (Yeo et al., Ann Surg 222:580-588 (1995); discussion 588-592). Indeed, the detection of PDAC or high-grade precursors in high-risk patient groups (e.g., hereditary cancer syndromes, chronic pancreatitis, and new-onset diabetes) represents a critical unmet need in the cancer diagnostic portfolio (Brentnall et al., Ann. Intern. Med. 131:247-255 (1999); Canto et al., Clin. Gastroenterol. Hepatol. 2:606-621 (2004)).
Currently, serum CA-19-9 is the clinically used biomarker; however, it lacks the sensitivity needed to detect early-stage PDAC (Goggins, J. Clin. Oncol. 23:4524-4531 (2005)). In addition, cross-sectional abdominal imaging has proven to be unreliable to detect early-stage PDAC in high-risk patients (Pelaez-Luna et al., Am J Gastroenterol 102:2157-2163 (2007)).
Thus a high priority in this field of medicine is the identification of biomarkers for the development of binding ligands as diagnostics, such as imaging probes for detecting pre-neoplastic/early invasive lesions and for use in treatments.